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1.
Drug Des Devel Ther ; 15: 3349-3378, 2021.
Article in English | MEDLINE | ID: covidwho-1352763

ABSTRACT

Dalbavancin is a novel, long-acting lipoglycopeptide characterized by a long elimination half-life coupled with excellent in vitro activity against multidrug-resistant Gram-positives. Although it is currently approved only for the treatment of acute bacterial skin and skin structure infections, an ever-growing amount of evidence supports the efficacy of dalbavancin as a long-term therapy in osteomyelitis, prosthetic joint infections, endocarditis, and bloodstream infections. This article provides a critical reappraisal of real-world use of dalbavancin for off-label indications. A search strategy using specific keywords (dalbavancin, osteomyelitis, endocarditis, long-term suppressive therapy, bloodstream infection, pharmacokinetic/pharmacodynamic profile) until April 2021 was performed on the PubMed-MEDLINE database. As for other novel antibiotics, a conundrum between approved indications and potential innovative therapeutic uses has emerged for dalbavancin as well. The promising efficacy in challenging scenarios (i.e., osteomyelitis, endocarditis, prosthetic joint infections), coupled with the unique pharmacokinetic/pharmacodynamic properties, makes dalbavancin a valuable alternative to daily in-hospital intravenous or outpatient antimicrobial regimens in the treatment of long-term Gram-positive infections. This makes dalbavancin valuable in the current COVID-19 scenario, in which hospitalization and territorial medicine empowerment are unavoidable.


Subject(s)
Ambulatory Care , Anti-Bacterial Agents/therapeutic use , COVID-19 , Gram-Positive Bacterial Infections/drug therapy , Off-Label Use , Patient Participation , Teicoplanin/analogs & derivatives , Algorithms , Anti-Bacterial Agents/adverse effects , Anti-Bacterial Agents/pharmacokinetics , Clinical Decision-Making , Decision Support Techniques , Gram-Positive Bacterial Infections/diagnosis , Gram-Positive Bacterial Infections/microbiology , Humans , Teicoplanin/adverse effects , Teicoplanin/pharmacokinetics , Teicoplanin/therapeutic use , Treatment Outcome
3.
Cell Res ; 31(1): 17-24, 2021 01.
Article in English | MEDLINE | ID: covidwho-953056

ABSTRACT

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic worldwide. Currently, however, no effective drug or vaccine is available to treat or prevent the resulting coronavirus disease 2019 (COVID-19). Here, we report our discovery of a promising anti-COVID-19 drug candidate, the lipoglycopeptide antibiotic dalbavancin, based on virtual screening of the FDA-approved peptide drug library combined with in vitro and in vivo functional antiviral assays. Our results showed that dalbavancin directly binds to human angiotensin-converting enzyme 2 (ACE2) with high affinity, thereby blocking its interaction with the SARS-CoV-2 spike protein. Furthermore, dalbavancin effectively prevents SARS-CoV-2 replication in Vero E6 cells with an EC50 of ~12 nM. In both mouse and rhesus macaque models, viral replication and histopathological injuries caused by SARS-CoV-2 infection are significantly inhibited by dalbavancin administration. Given its high safety and long plasma half-life (8-10 days) shown in previous clinical trials, our data indicate that dalbavancin is a promising anti-COVID-19 drug candidate.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Antiviral Agents , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Teicoplanin/analogs & derivatives , Animals , Antiviral Agents/pharmacokinetics , Antiviral Agents/pharmacology , Caco-2 Cells , Chlorocebus aethiops , Disease Models, Animal , Humans , Mice , Mice, Transgenic , Protein Binding/drug effects , Teicoplanin/pharmacokinetics , Teicoplanin/pharmacology , Vero Cells
4.
Ther Drug Monit ; 42(2): 165-168, 2020 04.
Article in English | MEDLINE | ID: covidwho-11505

ABSTRACT

BACKGROUND: Dalbavancin, albeit indicated for the treatment of skin structure infections, is used for a much wider range of infections. This drug is characterized by a long half-life (more than 200 hours), a favorable safety profile, and an activity against a wide array of gram-positive organisms, including several strains of Staphylococci and Enterococci. METHODS: In this study, we presented 3 cases of critically ill patients treated with dalbavancin. All patients were therapeutically monitored for plasma dalbavancin concentrations; ultrafiltrate dalbavancin concentrations were assessed in a patient undergoing continuous renal-replacement therapy. Dalbavancin concentrations were measured using a validated liquid chromatographic method coupled with mass spectrometry. RESULTS: All 3 severely ill patients experiencing necrotizing fasciitis were successfully treated during the acute phase with dalbavancin. Dalbavancin clearance in patient 3 (0.334 L/h) was considerably increased compared with values measured in the other 2 patients (0.054 and 0.075 L/h) and with data reported in the literature (0.04-0.06 L/h). CONCLUSIONS: Our case reports presented preliminary evidence that dalbavancin can be considered a therapeutic option for necrotizing fasciitis in intensive care unit patients. The role of hypoalbuminemia during dalbavancin exposure merits further investigation.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Critical Illness , Drug Monitoring/methods , Fasciitis, Necrotizing/drug therapy , Teicoplanin/analogs & derivatives , Adult , Anti-Bacterial Agents/pharmacokinetics , Half-Life , Humans , Male , Metabolic Clearance Rate , Microbial Sensitivity Tests , Middle Aged , Severity of Illness Index , Teicoplanin/pharmacokinetics , Teicoplanin/therapeutic use
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